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Selective antagonists at serotonin 5-HT 6 receptors (5-HT 6 R) improve memory performance in rodents and are currently under clinical investigations. If blockade of 5-HT 6 R is known to increase glutamate release, only two studies have so far demonstrated an interaction between 5-HT 6 R and glutamate transmission, but both, using the non-competitive NMDA antagonist MK-801, insensitive to variations of glutamate concentrations. In a place recognition task, we investigated here in mice the role of glutamate transmission in the beneficial effects of 5-HT 6 R blockade (SB-271046). Through the use of increasing intervals (2, 4 and 6h) between acquisition and retrieval, we investigated the time-dependent impact of two different glutamatergic modulators. NMDAR-dependant glutamate transmission (NMDA Receptors) was either blocked by the competitive antagonist at NMDAR, CGS 19755, or potentiated by the glycine transporter type 1 (GlyT1) inhibitor, NFPS. Results showed that neither SB-271046, nor CGS 19755, nor NFPS, alter behavioural performances after short intervals, i.e. when control mice displayed significant memory performances (2h and 4h) (respectively 10, 3, and 0.625mg.kg -1 ). Conversely, with the 6h-interval, a situation in which spontaneous forgetting is observed in control mice, SB-271046 improved recognition memory performances. This beneficial effect was prevented when co-administered with either CGS 19755 or NFPS, which themselves had no effect. Interestingly, a dose-dependent effect was observed with NFPS, with promnesic effect observed at lower dose (0.156mg.kg -1 ) when administrated alone, whereas it did no modify promnesic effect of SB-271046. These results demonstrate that promnesiant effect induced by 5-HT 6 R blockade is sensitive to the competitive blockade of NMDAR and underline the need of a fine adjustment of the inhibition of GlyT1. Overall, our findings support the idea of a complex crosstalk between serotonergic and glutamatergic systems in the promnesic properties of 5-HT 6 R antagonists., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Bariatric surgery underwent a dramatic change in the past decade in France. The objective of this study was to examine elective bariatric surgical procedures from 2005 to 2011 in France and to determine trends in the use of the procedure., Methods: Data were extracted from the National Hospital Database. All admissions involving a bariatric surgery procedure were included. Procedures authorized by the Public Health Authority for the treatment of morbid obesity, including the adjustable gastric banding (AGB), vertical banded gastroplasty (VBG), gastric bypass (GB), sleeve gastrectomy (SG), and biliopancreatic diversion (BPD), either by laparotomic or laparoscopic approach, were retrieved. Revisional procedures, such as band removal or repositioning, band changing, and access device revisions, were also evaluated., Results: We observed a 2.5-fold increase in bariatric procedures, from 12,800 in 2005 to 31,000 in 2011. Sleeve gastrectomy and gastric bypass became the most common bariatric procedures in France in 2011, whereas adjustable gastric banding has been decreasing since 2007. During the analysis period, about 50,000 revisional procedures were performed. The number of hospitals (private or public) providing bariatric surgery has considerably increased. However, most of the activity remains confined to a small number of centers, as 50% of all bariatric surgeries are carried out in 12% of hospitals. Bariatric procedures are predominantly performed in private hospitals., Conclusions: In France the number of bariatric procedures increased considerably between 2005 and 2011. The type of procedures changed, with a constant decrease of AGB and an important increase of SG and GB. Most bariatric procedures are still performed in low volume activity hospitals and in private hospitals., (© 2013 American Society for Bariatric Surgery Published by American Society for Metabolic and Bariatric Surgery All rights reserved.)

Background: In Africa, lactational amenorrhea is the major reason for birth spacing., Objective: We studied whether the early introduction of complementary food to infants is associated with an increased risk of menstruation resumption in rural African women., Design: Senegalese women (n = 855) were included at 2-3 mo postpartum and followed up at 4-5 and 6-7 mo in dispensaries. A subsample of 502 women were followed up at 9-10 mo and twice yearly at home thereafter. Risk factors for menstruation resumption were assessed with logistic regression, with control for maternal parity, occupation, education, postpartum body mass index, child sex and weight-for-age, and season., Results: The risk of menstruation resumption was 4.2% (95% CI: 2.8%, 5.6%) at 6-7 mo and 6.5% (4.0%, 8.9%) at 9-10 mo. Compared with the introduction of complementary food after 6-7 mo, introduction at 2-3, 4-5, or 6-7 mo was associated with a greater odds of menstruation resumption at 6-7 mo [odds ratios (ORs): 5.08 (1.01, 25.5), 6.00 (1.29, 27.4), and 4.45 (0.96, 20.6; NS), respectively]. Introduction of food at 4-5 or 6-7 mo compared with that after 6-7 mo was associated with significantly greater odds of menstruation resumption at 6-7 mo (5.13; 1.16, 22.6) but not at 9-10 mo (3.07; 0.65, 14.4; NS) or year 2., Conclusion: Child age at introduction of complementary food was significantly associated with the odds of menstruation resumption at 6-7 mo postpartum.

The p53 protein is a tumor suppressor that protects the organism against malignant consequences of DNA damage. Interaction of p53 with numerous cellular or viral proteins regulates its functional activity either positively or negatively. An approach leading to identification of such protein interactions directly in a cell extract could be of help in the development of screening assays to search for drugs acting on p53 in its cellular environment, either by disrupting its association with inhibitory proteins or by increasing its affinity for activating proteins. We show that the homogeneous time-resolved fluorescence (HTRF) assay based on the time-resolved amplified cryptate emission (TRACE) technology allows identification of such an interaction by simply adding a mixture of two labeled monoclonal antibodies, directly in a cellular extract. We validate this assay by studying p53/SV40-LTAg interactions. The antibodies directed against genuine p53 and SV40-LTAg epitopes were labeled with europium cryptate (donor) and XL665, a crosslinked allophycocyanin (acceptor), respectively. We demonstrated that a nonradiative energy transfer occurs between labeled antibodies only when p53 interacts with SV40-LTag, which opens up the possibility of extending this approach to other p53 partners to search for drugs that restore p53 tumor-suppressor activity.

Background: Prolonged breast-feeding is frequently associated with malnutrition in less-developed countries, even after adjustment for socioeconomic confounders. However, in rural Senegal, breast-feeding is prolonged when the child is stunted., Objective: We aimed to test whether the lower height-for-age of children weaned late is explained by their height before weaning or whether prolonged breast-feeding is associated with impaired growth., Design: A cohort of 443 Senegalese children recruited from dispensaries at 2 mo of age were visited in their homes at 6-mo intervals when they were approximately 1.5 to 3 y of age. Weight, length, arm circumference, and triceps skinfold thickness were measured. Six-month increments were analyzed in relation to breast-feeding (breast-fed compared with weaned children or breast-feeding duration), season, and maternal housing with use of multiple linear regression., Results: The mean duration of breast-feeding was 24.1 mo (quartiles 1 and 3: 21.9 and 26.4). Height-for-age at the age of 3 y was negatively associated with age at weaning (P < 0.01), but this association disappeared after adjustment for height-for-age in infancy. Length increments were significantly greater in both the second and third years of life in children breast-fed for longer durations (P < 0.05) and tended to be greater in breast-fed than in weaned children in the second year of life (P = 0.05). In the third year of life, breast-fed children had greater length increments than did weaned children in the subgroup with poor housing (P for interaction < 0.05). Growth in weight did not differ significantly according to breast-feeding., Conclusion: Prolonged breast-feeding improved linear growth, and the negative relation between height-for-age and duration of breast-feeding was due to reverse causality.

We describe here a competitive hybridization assay using TRACE technology which can be used for real-time monitoring of oligonucleotide hybridization. This assay quantifies all kinds of oligonucleotides in biological fluids without extraction. The assay makes use of two different probes and involves a fluorescent transfer process. As fluorescence measurements are not destructive, they can be sequentially repeated, thereby allowing comparison of the hybridization kinetics and binding strength of chemically modified backbone oligonucleotides (>0.5 nM) in biological media. The assay was validated for pharmacokinetic analysis of phosphodiester and phosphorothioate oligonucleotides in plasma and in different organs (liver, kidneys, lungs, spleen) at low concentrations (0.4 mg/kg, corresponding to clinical doses). Respective sensitivities for phosphodiester and phosphorothioate were 0.2 and 0.8 pmol/ml in plasma and 2 and 8 pmol/g in tissues, which allow to recover intact phosphorothioate sequences in some organs even after 24 h., (Copyright 2000 Academic Press.)